HIGH RESOLUTION HYBRID FT-ICR MASS SPECT: CANCER, PROSTATE CANCER

高分辨率混合 FT-ICR 质谱：癌症、前列腺癌

• 批准号: 7335344
• 负责人: Joseph A Loo
• 金额: $ 12.45万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7335344
• 关键词: ions; prostate neoplasms; proteins

This subproject is one of many research subprojects utilizing the resources provided by a Shared Instrumentation Grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the grant, which is not necessarily the institution for the investigator. DESCRIPTION (PROVIDED BY APPLICANT): A high-resolution hybrid Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer with capabilities for top-down protein sequencing and rapid duty-cycle LC-tandem MS measurements for bottom- up proteomics is requested. This instrument will be a vital component to support the specific aims of over 11 NIH-funded projects. The projects involve a variety of protein structure/function-related research, including the determination of protein-protein and protein-ligand interactions, protein phosphorylation, and the identification of protein biomarkers for disease detection and prognosis. The research will impact a range of human health issues, including neurodegenerative diseases, such as Huntington's disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), respiratory illnesses, cardiovascular and inflammatory diseases, and cancer. The hybrid FT-ICR mass spectrometer will be capable of sub-2 parts-per-million mass measurement accuracy for both intact peptides/proteins and product ions derived from MS/MS experiments. It will include a storage trapping device for increased dynamic range and have capabilities for rapid data dependent LC-MS/MS, and a resolving power sufficient to measure the isotope distribution of large, intact proteins for improved mass accuracy. Unique to this system will be capabilities for electron capture dissociation (ECD) and infrared multiphoton dissociation (IRMPD), ion activation methods advantageous for top-down protein sequencing and identification/localization of post-translational modifications. ECD greatly improves the ability to dissociate intact proteins to derive complete sequence information, as well as holding the promise of detection of post-translational modifications. An instrument with these unique capabilities is not available currently at UCLA. The instrument will be a centerpiece and will be supported and administered by the newly-created Molecular Instrumentation Center at UCLA, and it will serve researchers from across the institution.

该子项目是利用 NIH/NCRR 资助的共享仪器补助金提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是资助机构，不一定是研究者的机构。描述（由申请人提供）：需要一种高分辨率混合傅里叶变换离子回旋共振 (FT-ICR) 质谱仪，具有自上而下的蛋白质测序功能和用于自下而上蛋白质组学的快速占空比 LC-串联 MS 测量功能。该工具将成为支持超过 11 个 NIH 资助项目的具体目标的重要组成部分。这些项目涉及各种与蛋白质结构/功能相关的研究，包括确定蛋白质-蛋白质和蛋白质-配体相互作用、蛋白质磷酸化以及用于疾病检测和预后的蛋白质生物标志物的鉴定。该研究将影响一系列人类健康问题，包括神经退行性疾病，如亨廷顿舞蹈病、阿尔茨海默病、帕金森病和肌萎缩侧索硬化症（ALS）、呼吸系统疾病、心血管和炎症疾病以及癌症。混合 FT-ICR 质谱仪对于完整的肽/蛋白质和来自 MS/MS 实验的产物离子的质量测量精度将达到百万分之二以下。它将包括一个用于增加动态范围的存储捕获装置，并具有快速数据依赖型 LC-MS/MS 的能力，以及足以测量大型完整蛋白质的同位素分布的分辨率，以提高质量精度。该系统的独特之处在于电子捕获解离（ECD）和红外多光子解离（IRMPD）功能，离子激活方法有利于自上而下的蛋白质测序和翻译后修饰的识别/定位。 ECD 极大地提高了解离完整蛋白质以获得完整序列信息的能力，并有望检测翻译后修饰。目前加州大学洛杉矶分校还没有具有这些独特功能的仪器。该仪器将成为核心，并将由加州大学洛杉矶分校新创建的分子仪器中心提供支持和管理，并将为整个机构的研究人员提供服务。